tbuckley/cabot-search huggingface dataset:
5593300 INVESTIGATIONS OF KIDNEY DYSFUNCTION-RELATED GENE VARIANTS IN SICKLE CELL DISEASE PATIENTS IN CAMEROON (SUB-SAHARAN AFRICA)
Authors: V.B. NGO BITOUNGUI, S.B. Belinga Suzanne, K.M. Khuthala Mnika, V.N. Victoria Nembaware, R.E. René ESSOMBA, A.W. Ambroise Wonkam
Journal: HemaSphere (2023)

Background: Renal dysfunctions are associated with increased morbidity and mortality in sickle cell disease (SCD). Early detection and subsequent management of SCD patients at risk for renal failure and dysfunctions are essential, however, predictors that can identify patients at risk of developing renal dysfunction are not fully understood. Aims: the aims of the study were: to employ a multi-factorial approach to investigate genetic factors and also to explore the contribution of socio-demographic, anthropometric, clinical and haematological variables associated to renal abnormalities in SCD patients in Cameroon. Methods: In this study, we have investigated the association of 31 known kidney dysfunctions-related variants detected in African Americans from multi-ethnic genome wide studies (GWAS) meta-analysis to kidney-dysfunctions in a group of 413 Cameroonian patients with SCD. Systems level bioinformatics analyses were performed, employing protein-protein interaction networks to further interrogate the putative associations. Results: Up to 61% of these patients had micro-albuminuria, 2.4% proteinuria, 71% glomerular hyperfiltration, and 5.9% had renal failure. Six variants are significantly associated with the two quantifiable phenotypes of kidney dysfunction (eGFR and crude-albuminuria): A1CF-rs10994860 (P = 0.02020), SYPL2-rs12136063 (P = 0.04208), and APOL1 (G1)-rs73885319 (P = 0.04610) are associated with eGFR; and WNT7A-rs6795744 (P = 0.03730), TMEM60-rs6465825 (P = 0.02340), and APOL1 (G2)-rs71785313 (P = 0.03803) observed to be protective against micro-albuminuria. We identified a protein-protein interaction sub-network containing three of these gene variants: APOL1, SYPL2, and WNT7A, connected to the nuclear factor NF-kappa-B p105 subunit (NFKB1), revealed to be essential and might indirectly influence extreme phenotypes. Interestingly, clinical variables, including body mass index (BMI), systolic blood pressure, vaso-occlusive crisis (VOC), and haemoglobin (Hb), explain better the kidney phenotypic variations in this SCD population. Conclusion: This study highlights a strong contribution of haematological indices (Hb level), anthropometric variables (BMI, blood pressure), and clinical events (i.e., vasoocclusive crisis) to kidney dysfunctions in SCD, rather than known genetic factors. Only 6/31 characterised gene-variants are associated with kidney dysfunction phenotypes in SCD samples from Cameroon. The data reveal and emphasise the urgent need to extend GWAS studies in populations of African ancestries living in Africa, and particularly for kidney dysfunctions in SCD. Keywords: sickle cell disease, kidney dysfunctions, gene variants, cameroon, Africa References 1. Ngo-Bitoungui et al Frontiers in Genetics, section Genomic Medicine, 2021; 2. Aloni et al Clinical Kidney Journal 10,2017; 479–486.
5613165 INVESTIGATING VARIANTS ASSOCIATED WITH QUANTITATIVE RED BLOOD CELL PHENOTYPES FROM TOPMED PREDICTIONS IN AFRICAN SICKLE CELL DISEASE POPULATIONS.
Authors: N. Samie, K. Mnika, K. Esoh, V. Nembaware, A. Wonkam
Journal: HemaSphere (2023)

Background: Sickle cell disease (SCD) is caused by a single point mutation (c.20A>T, p.Glu6Val), which results in the formation of mutant haemoglobin S (HbS) instead of haemoglobin A (HbA). It is a life-long inherited recessive disorder that predominantly affects people of African, Indian, and Mediterranean descent. The polymerisation of HbS within red blood cells (RBCs) is the primary pathophysiological alteration in SCD, which results in the sickle-shape of RBCs. Sickle-shaped RBCs are more prone to haemolysis and blocking blood flow, resulting in anaemia and painful episodes. Haematological indices including haematocrit (HCT), haemoglobin concentration (Hb), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), red blood cell width (RDW) and RBC count indicate the size, development, and haemoglobin content of RBCs. Haematological indices are routinely measured as a means of monitoring SCD. A study recently found associations between 14 novel variants and haematological indices when using whole genome sequencing (WGS) data. The association between these variants and haematological indices have not yet been investigated in African SCD patients. This study aims to determine the associations between these variants and haematological indices in SCD patients from Cameroon and Senegal compared to non-SCD individuals. Aim: Investigating the association of 13 novel variants previously found in the Trans-Omics for Precision Medicine (TOPMed) project to haematological indices in African SCD patients. Methods: The 14 variants from the TOPMed study will be genotyped using a TaqMan Assay platform. Sanger sequencing will then be performed on 10% of the cohort to validate the TaqMan Assay result. The application R will be used for the descriptive statistics using sociodemographic, clinical, and haematological indices to evaluate the cases and controls. The Hardy-Weinberg Equilibrium will be used to ensure quality control. A linear regression analysis will be performed in R to determine the association between the variants and RBC phenotypes. Expected results: We are expecting to find an association between the SNPs and haematologocial indices. Conclusion: The variants of focus in this study were prioritized using WGS data, therefore capturing variants that are usually not included in GWAS arrays or imputation reference panels. The associations of the 13 novel variants with haematological indices have not yet been tested in African SCD populations. The results of this investigation could positively impact future studies into predictive modelling using haematological indices. References 1. Cardenes, N. et al., Blood, 2014; 123(18) 2. Chen, M.-H.et al., Cell, 2020; 182(5) 3. Hu, Y. et al., The American Journal of Human Genetics, 2021; 108(5) 4. Xu, M. et al., PLOS Computational Biology, 2014; 13(10)
Comprehensive benchmark and architectural analysis of deep learning models for nanopore sequencing basecalling
Authors: Marc Pagès-Gallego, Jeroen de Ridder
Journal: Genome biology (2023)

Nanopore-based DNA sequencing relies on basecalling the electric current signal. Basecalling requires neural networks to achieve competitive accuracies. To improve sequencing accuracy further, new models are continuously proposed with new architectures. However, benchmarking is currently not standardized, and evaluation metrics and datasets used are defined on a per publication basis, impeding progress in the field. This makes it impossible to distinguish data from model driven improvements.
5613019 THE CO-EXISTENCE OF SICKLE CELL DISEASE WITH NEUROFIBROMATOSIS: A CASE REPORT
Authors: K. Crombie, S. Simon, J. Brent
Journal: HemaSphere (2023)

Sickle Cell disease is an autosomal recessive disorder that occurs as a result of a point mutation in the haemoglobin beta gene found on chromosome 11p15. It affects approximately 1 in 2000 livebirths in the UK1. Neurofibromatosis Type 1 has an incidence of around 1:30002. Neurofibromatosis is caused by mutations in the NF1 gene found on chromosome 17. Although it can be inherited in an autosomal dominant fashion, in about 50 percent of individuals Neurofibromatosis occurs spontaneously2. We present the case of 10 year old girl of Caribbean descent who was born prematurely at 27 weeks gestation. She was diagnosed with Sickle Cell disease on routine newborn screening. In infancy she had chronic lung disease, poor growth, and developmental delay. Throughout childhood she has required numerous prolonged admissions with vaso-occlusive crisis and chest infections. Her clinical condition is prone to rapid decompensation and has frequently been transferred to intensive care for management of both significant chest infections and acute chest syndrome. Her growth continues to follow the 0.4th centile. She also has learning difficulties and features of autism. These complications were initially thought to be related to her prematurity and sickle cell disease. However, more recently she developed an increasing number of freckles to her torso. She has multiple café au lait patches with axillary and groin freckling, meeting the diagnostic criteria for Neurofibromatosis 1. This is likely to have occurred as a de novo mutation as no other family members are affected. Despite the common occurrence of both these genetic disorders, a literature search found there has only been one previous published case report worldwide of a patient with both Sickle Cell disease and Neurofibromatosis Type 13. In this case report we describe the patient’s clinical course and management to date, and consider the need to look for additional diagnoses in patients with multiple complications. References 1. BMJ Best Practice (2021) Sickle cell anaemia. BMJ Publishing Group 2. Evans et al (2010) Am J Med Genet A. 2010;152A(2):327 3. Alanzi et al, Journal of Applied Haematology, 2019, 10(1):33
5613391 SUBCLINICAL NEPHROTOXICITY IN PATIENTS WITH BETA-THALASSEMIA: ROLE OF URINARY KIDNEY INJURY MOLECULE
Authors: M. Zakaria, T.H. Hassan, O. Nafea, S. El Gebaly, H. Salah
Journal: HemaSphere (2023)

Background: Improved survival in thalassemic patients has led to the emergence of previously unrecognized complications, such as renal disease. Aim: We aimed to investigate the role of urinary kidney injury molecule-1 (KIM-1) in detection of subclinical nephrotoxicity in patients with Beta-thalassemia (β-TM) in relation to chelation therapy and to correlate the urinary KIM-1 level with other clinical and laboratory findings. Methods: We conducted a cross-sectional study on 66 thalassemic patients. Their ages range from 7 to 22 years. Routine kidney indices and novel urinary KIM/creatinine ratio (UKIM-1/Cr) were measured. Estimated glomerular filtration rate (eGFR) was calculated. Results: Results indicate that the level of serum creatinine was significantly higher in patients on deferasirox therapy than patients on deferoxamine and deferiprone therapy [median(IQR), 0.85(0.63–0.99), 0.50(0.34–0.58) and 0.44(0.36–0.45)] mg/dL, respectively, p < 0.001]. The median(IQR) level of eGFR was significantly lower in patients on deferasirox therapy than patients on deferoxamine and deferiprone therapy [63.3(56.5–92.1), 117.3(91.9–162) and 136.7(109.4–157.6)] ml/min/1.73 m2, respectively, p < 0.001]. The mean level of UKIM-1/Cr was significantly higher in patients on deferasirox therapy than patients on deferoxamine and deferiprone therapy (7.0 ± 1.9, 4.1 ± 1.7 and 4.2 ± 1.5) ng/mg creatinine, respectively, p < 0.001). Conclusion: We concluded that urinary KIM-1 is an early predictive biomarker for decline in eGFR in patients with β-TM on deferasirox therapy. The appropriate chelation therapy and good monitoring of those patients are intensely needed for early detection of renal dysfunction and timely intervention. References 1. Aldudak et al,Pediatric Nephrology 2000;15:109. 2. Ali et al, Saudi Journal of Kidney Diseases and Transplantation 2008;19: 206. 3. Bagshaw and Gibney, Critical Care Medicine 2008; 36: S152.
5612560 A MONITORING AND EVALUATION FRAMEWORK AND ASSOCIATED TOOLS FOR THE SICKLEINAFRICA CONSORTIUM
Authors: V. Nembaware, M. Paidamoyo Bodzo, M. Nkanyemka, I. Minja, J. Makani, N. Mulder, A. Wonkam
Journal: HemaSphere (2023)

1Victoria Nembaware, 1Paidamoyo Bodzo, 2Malula Nkanyemka, 2Irene Minja, 2Julie Makani, 3Nicola Mulder, 1,4Ambroise Wonkam on behalf of the SickleInAfrica Consortium 1Division of Human Genetics, Department of Pathology, University of Cape Town, Cape Town, South Africa 2Sickle Cell Programme, Department of Haematology and Blood Transfusion, Muhimbili University of Health and Allied Sciences 3Computational Biology Division, Faculty of Health Sciences, Anzio Road, Observatory, Cape Town, South Africa 1,4McKusick-Nathans Institute of Genetic Medicine and Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Background: The SickleInAfrica consortium aims facilitate research in Sickle Cell Disease (SCD) and the subsequent translation of this research into healthcare and health outcomes. SickleInAfrica is made up of three initiatives: Sickle Africa Data Coordinating Center (SADaCC) and the Sickle Pan-African Research Consortium (SPARCO), which has a clinical coordinating center (CCC) in Tanzania and SPARCO research sites based in seven countries: Ghana, Nigeria, Mali, Tanzania, Uganda, Zimbabwe and Zambia. To achieve its goals SickleInAfrica is creating a multi-country registry of over 30,000 SCD patients amongst other activities which include: skills development, development of standards of care, maintenance of a SCD Ontology, strengthening of infrastructure and addressing pertinent ethical, legal and social issues. A key challenge is the monitoring and evaluation of activities across the consortium in a consistent manner. Method: To maximize efforts and increase the likelihood of impact of this consortium we developed a consortium-wide outcome-based monitoring and evaluation plan which is informed by existing frameworks and lessons from existing consortia and research projects. In addition, we conducted stakeholder consultation during consortium meetings which were used to continually adjust the system. Most of the framework was imbedded into the consortium website to allow for seamless data collection. Results: We present SickleInAfrica activities and outline the corresponding monitoring and evaluation framework, associated indicators, dashboard and tools which are accessible via the SickleInAfrica website. The proposed framework was designed to be adaptable by other consortia and research initiatives. Summary and Conclusion: To facilitate large-scale monitoring and evaluation of consortium activities, we propose a framework which is mostly web-based. Once stable, such a framework and associated tools will be made available for use by similar initiatives. Reference 1. Makani et al, Lancet Haematol. 2020; 7(2):e98-e9
5610325 VARIABILITY OF OXYGENSCAN PARAMETERS ACCORDING TO THE TYPE OF THERAPY IN CHILDREN WITH SICKLE CELL DISEASE: PRELIMINARY DATA FROM A FEASIBILITY STUDY
Authors: G. Reggiani, M. Martella, V. Munaretto, I. Baido, M.P. Boaro, A. Biffi, L. Sainati, R. Colombatti
Journal: HemaSphere (2023)

Background: Sickle Cell Disease (SCD) is characterized by significant phenotypic variability even when the same causative mutation is present (1). Validated biomarkers for routine use in SCD, to evaluate phenotypic severity and predict the evolution of organ damage and response to different therapies, are currently lacking. Oxygenscan (function of the instrument Laser-assisted Optical Rotational Red Cell Analyser) is a novel physiological assay of red blood cells’ deformability at different oxygen tensions; it allows the measurement of parameters such as maximum/minimum elongation index e point of sickling (2,3). Aims: This feasibility study aims at preliminarily evaluating the variability of the point of sickling, as a possible biomarker in SCD, with respect to different clinical conditions and types of treatment. Methods: We’ve prospectively gathered peripheral blood samples of pediatric patients with SCD followed in the Veneto Region Pediatric Sickle Cell Disease Reference Center of Padua University Hospital. The Oxygenscan test has been repeated twice for each sample. Results: We’ve analysed 67 blood samples of 48 pediatric patients with SCD (36 HbSS, 5 HbSbeta0, 7 HbSC). Patients were not receiving a disease-modifying therapy (n.11) or were on hydroxyurea (HU) (n.32), on HU and chronic transfusion regimen (n.2), HU and crizanlizumab (n.2), or after HSCT (n.2, one of them had been evaluated also before HSCT). Parameters obtained by Oxygenscan seem to vary according to the type of treatment received by patients (Figure 1).Conclusion: A higher number of samples and further analyses will be necessary to investigate a possible relationship between the point of sickling and clinical data such as the evolution of organ damage and response to different types of treatment. References 1. Habara A, Steinberg MH. Minireview: Genetic basis of heterogeneity and severity in sickle cell disease. Exp Biol Med (Maywood). 2016 Apr;241(7):689-96. 2. Rab MAE, van Oirschot BA, Bos J, et al. Characterization of Sickling During Controlled Automated Deoxygenation with Oxygen Gradient Ektacytometry. J Vis Exp. 2019;(153):10.3791/60213. 3. Sadaf A, Seu KG, Thaman E, et al. Automated Oxygen Gradient Ektacytometry: A Novel Biomarker in Sickle Cell Anemia. Front Physiol. 2021;12:636609.
5610614 ASSESSING PHYSICAL, SOCIAL AND EMOTIONAL IMPACT OF SICKLE CELL DISEASE IN PORTUGUESE PATIENTS: AN OBSERVATIONAL, MULTICENTER STUDY (ASCEND)
Authors: C.S. Christopher Saunders, M.M. Marinela Major, A.T. Ana Tomé, J.M. Joana Martins, M.M.D. Maria Manuel Deveza, T.M.M. Tabita Magalhães Maia, C.B. Celeste Bento, I.F. Inês Fonseca, I.M. Inês Moital, D.B. Daniel Brás
Journal: HemaSphere (2023)

Background: Sickle cell disease (SCD) is a chronic, multisystem autosomal recessive blood disorder that is characterized by painful episodes caused by vaso-occlusion. SCD patients can face social, economic and academic challenges, as well as barriers to accessing quality heath care. Evidence about the impact of SCD and related treatments on the lives of patients is lacking, with a broad definition of health as a combination of physical, mental and social well-being. The purpose of this observational study is to characterize the physical, social and emotional impact of SCD on adult patients with confirmed diagnosis and to characterize patient pathway in the healthcare system. Objectives: The primary objective of ASCEND is to characterize the physical impact of SCD on patients, through collection of PROs that will assess the impact of pain and disease complications in patients’ QoL. As secondary objectives the study aims to characterize SCD patients’ demographics and clinical history, as well as to describe the social and emotional impact of SCD on patients; to describe SCD patient pathway in the healthcare system. In this abstract the authors intend to describe the results obtained for QoL assessment through PRO questionnaires Methods: ASCEND is non-interventional cross-sectional study of 2 cohorts of SCD adult patients with SCD. The study sample is 200 (recruited by hospital sites) + 50 patients (recruited by patient association). PRO questionnaires include both EQ-5D-5L and ASCQ-Me (Pain Episodes Frequency and Severity). Portuguese patients and Social Studies investigators participated in the validation process. Results: Study recruitment is terminating in the current week as 194 have been included already. We expect to have QoL results evaluated through EQ-5D-5L and ASQC-Me for 200 patients by mid September 2022, in due time to be presented in ASCAT. Conclusions: Conclusions will be elaborated upon data analyses References 1. Osunkwo I, Andemariam B, Minniti CP, Inusa BPD, El Rassi F, Francis-Gibson B, et al. Impact of sickle cell disease on patientsʼ daily lives, symptoms reported, and disease management strategies: Results from the international Sickle Cell World Assessment Survey (SWAY). American Journal of Hematology. 2021;96(4):404-17; 2. Piel FB, Steinberg MH, Rees DC. Sickle Cell Disease. N Engl J Med. 2017;376(16):1561-73
5595849 THE GUT MICROBIOME AND HYDROXYUREA EFFECT ON SICKLE CELL DISEASE CHILDREN FROM ANGOLA
Authors: M. Brito, M. Delgadinho, C. Ginete, B. Santos, J. Vasconcelos
Journal: HemaSphere (2023)

Background: Sickle cell disease (SCD) is an inherited hematological disorder and a serious global health problem, affecting between 20 and 25 million people worldwide [1]. In the Sub-Saharan Africa, where it is more prevalent, it contributes up to 90% of under-5 mortality [2]. Although hydroxyurea (HU) is the leading treatment for these patients, its effects on the gut microbiome have not yet been explored. Some studies reported that gastroenteritis events were less frequent in SCA children taking HU and it also significantly improved the survival from pneumococcal infections [3,4]. HU may have a protective effect, not only by improving several hematological parameters but also by lowering the risk of some bacterial infections. Aims: In this context, the aim of this study was to investigate this association by characterizing the gut microbiome of an Angolan SCA pediatric population before and after 6 months of HU treatment and comparing with a control group of healthy siblings. Results: A total of 113 fecal samples were obtained and sequenced by NGS for the 16S rRNA gene (V3-V4 regions), which corresponded to 40 children in the control and before HU groups and 33 after HU, aged between 4-12 years old. Our findings revealed that these three groups exhibit some notable differences, especially within Lachnospiraceae and Ruminococcaceae family. After HU treatment there was an increase of several beneficial bacteria, such as: Blautia coccoides (p=0.009), Blautia luti (p<0.001), Blautia faecis (p=0.008), Bifidobacterium longum (p=0.011), Dorea formicigenerans (p<0.001), Dorea massiliensis (p=0.003), Eubacterium halii (p=0.004), Elusimicrobium spp (p=0.032), Ruminococcus callidus (p=0.037), Ruminococcus faecis (p=0.012), Roseburia spp (p=0.050) and Subdoligranulum variabile (p=0.009). Most of those OTUs are SCFAs producing species, having butyrate or propionate as end-products of bacterial metabolism, both exhibiting anti-inflammatory properties. Moreover, children before HU had higher abundance of bacteria considered pathogenic, like E. coli (p=0.001), Clostridiun_g24 (p=0.039) and H. influenzae (p=0.050). Conclusion: Overall, this study provides the first evidence of the HU effect on the gut microbiome and provides a rationale for further research for developing treatments to reduce gut microbiota-driven inflammation, which may attenuate the dysbiosis and chronic symptoms experienced by these patients. This work was supported by FCT/Aga Khan (project nº330842553) and FCT/MCTES (UIDB/05608/2020 and UIDP/05608/2020) –H&TRC. References 1. Mulumba, L.L. and Wilson, L., Int. J. Africa Nurs. Sci, 2015, 3:56–64 2. Kato, G.J. et al, Nat. Rev. Dis. Prim. 2018; 4:18010. 3. Thornburg, C.D. et al, Blood, 2012; 120:4304–4310 4. Lebensburger, J.D. et al, Blood, 2012; 119:1915–192
Hepatic IDH2 regulates glycolysis and gluconeogenesis
Authors: Huawei Wang, Qing Xiong, Guangzhen He, Jun Tang, Li Sun, Siyuan Cheng, Mengting Ke, Shangyu Chen, Yong Hu, Jieyuan Feng, Linyang Song, Beier Tong, Zhengwei Zhang, Zhe Dai, Yancheng Xu
Journal: Metabolism (2023)
ChatGPT: when artificial intelligence replaces the rheumatologist in medical writing
Authors: Frank Verhoeven, Daniel Wendling, Clément Prati
Journal: Annals of the Rheumatic Diseases (2023)

In this editorial we discuss the place of artificial intelligence (AI) in the writing of scientific articles and especially editorials. We asked chatGPT « to write an editorial for Annals of Rheumatic Diseases about how AI may replace the rheumatologist in editorial writing ». chatGPT's response is diplomatic and describes AI as a tool to help the rheumatologist but not replace him. AI is already used in medicine, especially in image analysis, but the domains are infinite and it is possible that AI could quickly help or replace rheumatologists in the writing of scientific articles. We discuss the ethical aspects and the future role of rheumatologists.